Cloning of mouse BMAL2 and its daily expression profile in the suprachiasmatic nucleus: a remarkable acceleration of Bmal2 sequence divergence after Bmal gene duplication

Cloning of mouse BMAL2 and its daily expression profile in the suprachiasmatic nucleus: a remarkable acceleration of Bmal2 sequence divergence after Bmal gene duplication
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DOI:
10.1016/s0304-3940(01)01581-6
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发表时间:
2001-03
影响因子:
2.5
通讯作者:
T. Okano;M. Sasaki;Y. Fukada
T. Okano;M. Sasaki;Y. Fukada
中科院分区:
医学4区
文献类型:
--
作者:
T. Okano;M. Sasaki;Y. Fukada

文献摘要

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脑-肌-Arnt样蛋白2(Brain-Muscle-Arnt-Like-protein 2,BMAL 2; Arnt 4)是一种新近发现的碱性螺旋环螺旋-Per-Arnt-Sim(Helix-Loop-Helix-Per-Arnt-Sim,bHLH-PAS)转录因子,参与脊椎动物生物钟系统中自动调节反馈环的正向调节。在这项研究中,我们克隆的cDNA编码小鼠和大鼠BMAL 2(mBMAL 2和rBMAL 2)从小鼠中脑和大鼠-1成纤维细胞,分别。系统发育分析表明,脊椎动物Bmal 1和Bmal 2基因是由一个祖先Bmal 1基因(dCyc基因的脊椎动物直向同源物)的单基因重复产生的,Bmal 2的pums迄今为止被称为直向同源物。有趣的是,BMAL 2蛋白在复制后比BMAL 1蛋白发散快约20倍,这表明BMAL 1中保守但BMAL 2中不保守的尚未鉴定的功能。在小鼠下丘脑含有视交叉上核(哺乳动物的中枢昼夜节律振荡器)的下丘脑中,mBmal 2 mRNA在光-暗周期下全天组成性表达。
Brain-Muscle-Arnt-Like-protein 2 (BMAL2; Arnt4) (aryl hydrocarbon receptor nuclear translocator) is a recently identified basic Helix-Loop-Helix-Per-Arnt-Sim (bHLH-PAS) transcription factor, which contributes to a positive regulation of autoregulatory feedback loop in vertebrate circadian clock systems. In this study, we cloned cDNAs encoding mouse and rat BMAL2 (mBMAL2 and rBMAL2) from mouse midbrain and rat-1 fibroblast cells, respectively. A phylogenetic analysis strongly suggested that vertebrate Bmal1 and Bmal2 genes were generated by a single gene duplication of an ancestral Bmal gene, a vertebrate ortholog of dCyc gene, and that ‘BMAL2’s putatively termed so far are orthologous. Interestingly, BMAL2 proteins have diverged about 20-fold more rapidly than BMAL1 proteins after the duplication, suggesting an as-yet-unidentified function conserved in BMAL1 but not in BMAL2. mBmal2 mRNA was constitutively expressed throughout the day under light–dark cycle in the mouse hypothalamus containing suprachiasmatic nucleus, the site of the central circadian oscillator in mammals.